Traditional Chinese medicine fermentation composition containing astragalus membranaceus and codonopsis pilosula, preparation method of traditional Chinese medicine fermentation composition and application of traditional Chinese medicine fermentation composition in preparation of medicine for treating diarrhea

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine fermentation composition containing astragalus membranaceus and codonopsis pilosula, a preparation method thereof and application of the traditional Chinese medicine fermentation composition in preparation of medicines for treating diarrhea. The traditional Chinese medicine fermented composition containing astragalus membranaceus and codonopsis pilosula comprises the following raw materials in parts by weight: 10-30 parts of astragalus membranaceus, 10-25 parts of codonopsis pilosula, 8-20 parts of poria cocos, 5-15 parts of smoked plum, 0.5-2 parts of lactobacillus acidophilus powder, 0.5-2 parts of lactobacillus casei powder and 0.5-2 parts of lactobacillus reuteri powder. Wherein the viable count of the lactobacillus acidophilus powder, the lactobacillus casei powder and the lactobacillus reuteri powder is greater than or equal to 1 * 10 < 9 > CFU / g. According to the traditional Chinese medicine composition, the synergistic interaction of the traditional Chinese medicine components and the probiotics is realized, the intestinal flora balance can be more effectively regulated, the intestinal mucosal barrier is repaired, and the intestinal inflammation is inhibited, so that the curative effect of treating diarrhea is remarkably improved.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a fermented traditional Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula, its preparation method, and its application in the preparation of drugs for treating diarrhea. Background Technology

[0002] Diarrhea is a common digestive system disease with a complex pathogenesis, often related to factors such as intestinal flora imbalance, impaired intestinal mucosal barrier, and abnormal inflammatory responses. Clinically, there are many types of drugs used to treat diarrhea, including chemically synthesized antidiarrheals, antibiotics, and probiotic preparations, but all have certain limitations. For example, chemically synthesized antidiarrheals are mostly symptomatic treatments and cannot fundamentally repair intestinal function; the overuse of antibiotics can further disrupt the balance of intestinal flora, leading to prolonged diarrhea; and single probiotic preparations have limited efficacy against diarrhea caused by complex etiologies.

[0003] Traditional Chinese medicine (TCM) has unique advantages in treating diarrhea, emphasizing holistic regulation and improving intestinal function through multiple targets. Astragalus membranaceus (Huangqi) tonifies Qi and Yang, strengthens the exterior and stops sweating; Codonopsis pilosula (Dangshen) tonifies the middle Jiao and benefits Qi, strengthens the spleen and lungs. Together, they enhance the body's immunity and repair the intestinal mucosal barrier. Poria cocos (Fuling) promotes diuresis and eliminates dampness, strengthens the spleen and calms the mind, improving intestinal water metabolism and relieving diarrhea symptoms. Ume plum (Wumei) is sour and astringent, possessing excellent antidiarrheal effects. The combination of these four herbs, balancing Qi tonification, spleen strengthening, dampness removal, and astringency, provides a sound TCM foundation for treating diarrhea.

[0004] Traditional Chinese medicine (TCM) fermentation technology combines traditional Chinese medicine with modern microbial fermentation techniques. Through the metabolic processes of microorganisms, the effective components of TCM are transformed, making them more easily absorbed by the human body. Simultaneously, the microbial metabolites can synergistically interact with the TCM components. However, current TCM fermentation technology still faces many unresolved technical bottlenecks, severely limiting efficacy enhancement: Existing research often focuses on the fermentation modification of single TCM herbs or simply mixing and fermenting multiple herbs, neglecting the impact of TCM compound formulations on the fermentation microenvironment. Furthermore, there is a lack of research on the synergistic effects of TCM components and microbial metabolites, making it difficult to maximize the synergistic efficacy of "TCM-microorganism". In addition, existing technologies often employ single-strain fermentation, resulting in a single metabolic pathway and failing to achieve comprehensive transformation of multiple TCM components, leading to increased costs but lower efficacy. Summary of the Invention

[0005] The purpose of this invention is to provide a traditional Chinese medicine fermentation composition containing Astragalus membranaceus and Codonopsis pilosula, its preparation method, and its application in the preparation of drugs for treating diarrhea.

[0006] To achieve the above objectives, the present invention provides the following technical solution: The first aspect of this invention provides a fermented traditional Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula, the fermented composition comprising the following raw materials in parts by weight: 10-30 parts Astragalus membranaceus, 10-25 parts Codonopsis pilosula, 8-20 parts Poria cocos, 5-15 parts Prunus mume, 0.5-2 parts Lactobacillus acidophilus powder, 0.5-2 parts Lactobacillus casei powder, and 0.5-2 parts Lactobacillus reuteri powder; wherein the viable count of the Lactobacillus acidophilus powder, Lactobacillus casei powder, and Lactobacillus reuteri powder is ≥1×10⁻⁶. 9 CFU / g.

[0007] Preferably, the viable count of the Lactobacillus acidophilus powder, Lactobacillus casei powder, and Lactobacillus reuteri powder is (1~5)×10⁻⁶. 9 CFU / g.

[0008] This invention constructs a synergistic formulation system of four traditional Chinese medicines: Astragalus membranaceus, Codonopsis pilosula, Poria cocos, and Prunus mume. Astragalus membranaceus and Codonopsis pilosula are rich in polysaccharides and saponins, providing a high-quality carbon source for probiotic fermentation, promoting bacterial colonization and proliferation, and also tonifying Qi and strengthening the spleen, enhancing the basic function of the intestinal mucosal barrier. Poria cocos promotes diuresis and eliminates dampness, regulating intestinal fluid metabolism and relieving water retention during diarrhea. Prunus mume contains natural organic acids, which can help lower the intestinal pH, adapting to the growth of probiotics, and also astringe the intestines to stop diarrhea, inhibiting excessive spasms of intestinal smooth muscle. The synergistic effect of these four herbs optimizes the fermentation microenvironment and directly targets intestinal pathological sites, thus better enhancing the antidiarrheal and intestinal motility-regulating effects of the composition.

[0009] A method for preparing the fermented traditional Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula includes the following steps: (1) Pretreatment of Chinese herbal raw materials: Astragalus membranaceus, Codonopsis pilosula, Poria cocos and Prunus mume are crushed separately, mixed evenly to obtain Chinese herbal mixed powder; water is added to the Chinese herbal mixed powder, soaked, heated to boiling, cooled, filtered, and the filtrate is collected to obtain Chinese herbal extract; (2) Preparation of fermentation medium: Add glucose, peptone and yeast extract to the Chinese herbal extract, stir evenly, adjust the pH value, sterilize and cool to obtain fermentation medium; (3) Inoculation and fermentation: Add Lactobacillus acidophilus powder and Lactobacillus reuteri powder to the fermentation medium and ferment under anaerobic conditions. Continue to add Lactobacillus casei powder to the fermentation medium and continue to ferment under anaerobic conditions. (4) Post-processing: After fermentation, the fermentation liquid is centrifuged, the supernatant is collected, and then freeze-dried under vacuum to obtain a traditional Chinese medicine fermentation composition containing Astragalus membranaceus and Codonopsis pilosula.

[0010] Preferably, 2-5% glucose, 0.5-1.5% peptone, and 0.3-0.8% yeast extract by mass of the traditional Chinese medicine extract are added to the extract.

[0011] Preferably, the pH value is adjusted to 6.0-7.0.

[0012] Preferably, Lactobacillus acidophilus powder and Lactobacillus reuteri powder are added to the fermentation medium and fermented at 35-38℃ under anaerobic conditions for 16-20 hours.

[0013] Preferably, Lactobacillus casei powder is added to the fermentation medium and fermented at 35-38℃ under anaerobic conditions for 24-28 hours.

[0014] This invention maximizes the synergistic function of probiotics by designing a precise gradient fermentation sequence. In the early stages of fermentation, *Lactobacillus acidophilus* and *Lactobacillus reuteri* powders are inoculated to create a suitable environment for the growth of subsequent strains; in the later stages, *Lactobacillus casei* powder is inoculated to increase the content of effective active components in the product. This sequence can alleviate nutrient competition and metabolic disorders among strains in the early stages, significantly improve the survival rate of probiotics and the utilization rate of metabolites, and enhance the regulatory effect on intestinal motility hyperactivity.

[0015] The third aspect of this invention provides the application of a fermented Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula in the preparation of a drug for treating diarrhea.

[0016] Preferably, a traditional Chinese medicine fermentation composition containing Astragalus membranaceus and Codonopsis pilosula is used as the active ingredient, and pharmaceutically acceptable excipients are added to prepare an oral preparation for the treatment of diarrhea; the oral preparation includes powder, granules, capsules, tablets, and oral liquid.

[0017] Preferably, the pharmaceutically acceptable excipients include one or more of fillers, disintegrants, binders, lubricants, flavoring agents, and preservatives; wherein the filler is one or more of starch, lactose, and mannitol; the disintegrant is one or more of crospovidone and sodium carboxymethyl starch; the binder is one or more of povidone and hydroxypropyl methylcellulose; the lubricant is one or more of magnesium stearate and talc; the flavoring agent is one or more of sucrose and steviol glycosides; and the preservative is one or more of potassium sorbate and sodium benzoate.

[0018] Compared with the prior art, the advantages and beneficial effects of the present invention are as follows: 1. This invention ferments four traditional Chinese medicines—Astragalus membranaceus, Codonopsis pilosula, Poria cocos, and Prunus mume—with Lactobacillus acidophilus, Lactobacillus casei, and Lactobacillus reuteri, achieving a synergistic effect between the medicinal components and probiotics. The medicinal components provide nutrients for the growth of probiotics, promoting their colonization in the intestines; the fermentation process of the probiotics transforms the macromolecular components of the medicinal materials into small-molecule active substances, improving the bioavailability of the medicinal components. The synergistic effect of these two processes more effectively regulates the balance of intestinal flora, repairs the intestinal mucosal barrier, and inhibits intestinal inflammation, thereby significantly improving the therapeutic effect on diarrhea.

[0019] 2. The preparation process of this invention is scientifically sound and reasonable. By optimizing the extraction conditions, fermentation conditions, and post-processing of traditional Chinese medicine, the activity of the effective components of traditional Chinese medicine and the metabolites of probiotics is preserved to the maximum extent, resulting in fermented products with high purity and good stability. Furthermore, this process is simple to operate, highly controllable, and suitable for industrial production.

[0020] 3. The raw materials of the fermented Chinese medicine products of this invention are all natural ingredients, with high safety and no obvious toxic side effects. They avoid the adverse reactions caused by the abuse of antibiotics and chemically synthesized drugs, and are suitable for long-term use, especially for children, the elderly and other patients with weak constitutions who suffer from diarrhea. Attached Figure Description

[0021] Figure 1 HE section of colon tissue from mice treated with the fermented Chinese medicine composition of Example 1.

[0022] Figure 2 HE section of colon tissue from mice treated with the fermented Chinese medicine composition of Example 2.

[0023] Figure 3 HE section of colon tissue from mice treated with the fermented Chinese medicine composition of Comparative Example 5.

[0024] Figure 4 HE section of colon tissue from mice treated with the fermented Chinese medicine composition of Comparative Example 6. Detailed Implementation

[0025] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0026] The bacterial strains used in the following embodiments of the present invention are all commercially available products: Lactobacillus acidophilus powder: Lactobacillus acidophilus JYLA-191; Lactobacillus casei powder: Lactobacillus casei L. Casei21; Lactobacillus reuteri powder: Lactobacillus reuteri JYLB-291, all from Shandong Zhongke Jiayi Bioengineering Co., Ltd.

[0027] Example 1 This embodiment provides a fermented traditional Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula. The fermented traditional Chinese medicine composition comprises the following raw materials in parts by weight: 20 parts Astragalus membranaceus, 15 parts Codonopsis pilosula, 12 parts Poria cocos, 10 parts Prunus mume, 1 part Lactobacillus acidophilus powder, 1 part Lactobacillus casei powder, and 1 part Lactobacillus reuteri powder; wherein the viable count of each powder is 1×10⁻⁶. 9 CFU / g.

[0028] The preparation method of the above-mentioned fermented Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula includes the following steps: (1) Pretreatment of Chinese herbal raw materials: Astragalus membranaceus, Codonopsis pilosula, Poria cocos and Prunus mume were pulverized to less than 80 mesh, and then mixed evenly according to the above weight parts to obtain Chinese herbal mixed powder; 10 times the weight of deionized water was added to the Chinese herbal mixed powder, soaked for 3 hours, heated to boiling for 40 minutes, cooled to room temperature, filtered through a 0.22 μm filter membrane, and the filtrate was collected to obtain Chinese herbal extract; (2) Preparation of fermentation medium: Add 3% glucose, 1.0% peptone and 0.4% yeast extract by mass of the above Chinese herbal extract to the Chinese herbal extract, stir evenly, adjust the pH value to 6.5, sterilize at 121℃ and 0.1MPa for 30 min, cool to 37℃ to obtain fermentation medium; (3) Inoculation and fermentation: Add Lactobacillus acidophilus powder and Lactobacillus reuteri powder to the fermentation medium and ferment at 37°C under anaerobic conditions for 18 hours. Stir once every 8 hours during the fermentation process, and stir for 15 minutes each time. Continue to add Lactobacillus casei powder to the fermentation medium and ferment at 37°C under anaerobic conditions for 25 hours. Stir once every 8 hours during the fermentation process, and stir for 15 minutes each time. (4) Post-processing: After fermentation, the fermentation liquid was centrifuged at 4℃ and 8000r / min for 15min and the supernatant was collected; then it was freeze-dried under vacuum to obtain the fermented Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula.

[0029] Example 2 This embodiment provides a fermented traditional Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula. The fermented traditional Chinese medicine composition comprises the following raw materials in parts by weight: 15 parts Astragalus membranaceus, 12 parts Codonopsis pilosula, 18 parts Poria cocos, 12 parts Prunus mume, 1 part Lactobacillus acidophilus powder, 1 part Lactobacillus casei powder, and 1 part Lactobacillus reuteri powder; wherein the viable count of each powder is 1×10⁻⁶. 9 CFU / g.

[0030] The preparation method of the above-mentioned fermented Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula includes the following steps: (1) Pretreatment of Chinese herbal raw materials: Astragalus membranaceus, Codonopsis pilosula, Poria cocos and Prunus mume were pulverized to less than 80 mesh, and then mixed evenly according to the above weight parts to obtain Chinese herbal mixed powder; 10 times the weight of deionized water was added to the Chinese herbal mixed powder, soaked for 3 hours, heated to boiling for 40 minutes, cooled to room temperature, filtered through a 0.22 μm filter membrane, and the filtrate was collected to obtain Chinese herbal extract; (2) Preparation of fermentation medium: Add 3% glucose, 1.0% peptone and 0.4% yeast extract by mass of the above Chinese herbal extract to the Chinese herbal extract, stir evenly, adjust the pH value to 6.5, sterilize at 121℃ and 0.1MPa for 30 min, cool to 37℃ to obtain fermentation medium; (3) Inoculation and fermentation: Add Lactobacillus acidophilus powder and Lactobacillus reuteri powder to the fermentation medium and ferment at 37°C under anaerobic conditions for 18 hours. Stir once every 8 hours during the fermentation process, and stir for 15 minutes each time. Continue to add Lactobacillus casei powder to the fermentation medium and ferment at 37°C under anaerobic conditions for 25 hours. Stir once every 8 hours during the fermentation process, and stir for 15 minutes each time. (4) Post-processing: After fermentation, the fermentation liquid was centrifuged at 4℃ and 8000r / min for 15min and the supernatant was collected; then it was freeze-dried under vacuum to obtain the fermented Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula.

[0031] Example 3 This embodiment provides a fermented traditional Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula. The fermented traditional Chinese medicine composition comprises the following raw materials in parts by weight: 28 parts Astragalus membranaceus, 22 parts Codonopsis pilosula, 10 parts Poria cocos, 6 parts Prunus mume, 1.5 parts Lactobacillus acidophilus powder, 1.5 parts Lactobacillus casei powder, and 1 part Lactobacillus reuteri powder; wherein the viable count of each powder is 1×10⁻⁶. 9 CFU / g.

[0032] The preparation method of the above-mentioned fermented Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula includes the following steps: (1) Pretreatment of Chinese herbal raw materials: Astragalus membranaceus, Codonopsis pilosula, Poria cocos and Prunus mume were pulverized to less than 80 mesh, and then mixed evenly according to the above weight parts to obtain Chinese herbal mixed powder; 10 times the weight of deionized water was added to the Chinese herbal mixed powder, soaked for 3 hours, heated to boiling for 40 minutes, cooled to room temperature, filtered through a 0.22 μm filter membrane, and the filtrate was collected to obtain Chinese herbal extract; (2) Preparation of fermentation medium: Add 3% glucose, 1.0% peptone and 0.4% yeast extract by mass of the above Chinese herbal extract to the Chinese herbal extract, stir evenly, adjust the pH value to 6.5, sterilize at 121℃ and 0.1MPa for 30 min, cool to 37℃ to obtain fermentation medium; (3) Inoculation and fermentation: Add Lactobacillus acidophilus powder and Lactobacillus reuteri powder to the fermentation medium and ferment at 37°C under anaerobic conditions for 18 hours. Stir once every 8 hours during the fermentation process, and stir for 15 minutes each time. Continue to add Lactobacillus casei powder to the fermentation medium and ferment at 37°C under anaerobic conditions for 25 hours. Stir once every 8 hours during the fermentation process, and stir for 15 minutes each time. (4) Post-processing: After fermentation, the fermentation liquid was centrifuged at 4℃ and 8000r / min for 15min and the supernatant was collected; then it was freeze-dried under vacuum to obtain the fermented Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula.

[0033] Example 4 This embodiment provides 100g of the fermented Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula prepared in Example 1, 200g of lactose, 20g of crospovidone, and 15g of povidone, mixed evenly, and a soft material was prepared by using an appropriate amount of ethanol as a wetting agent. The material was granulated by passing it through a 16-mesh sieve, dried, and then granulated by passing it through a 14-mesh sieve. 5g of magnesium stearate was added, mixed evenly, and packaged to obtain granules.

[0034] Comparative Example 1 The difference between this comparative example and Example 1 is that it lacks the inclusion of traditional Chinese medicine.

[0035] A fermented traditional Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula, comprising the following raw materials in parts by weight: 30 parts Astragalus membranaceus, 1 part Lactobacillus acidophilus powder, 1 part Lactobacillus casei powder, and 1 part Lactobacillus reuteri powder; wherein the viable count of each powder is 1×10⁻⁶. 9 CFU / g. Preparation method is the same as in Example 1.

[0036] Comparative Example 2 The difference between this comparative example and Example 1 is that it uses single probiotic fermentation.

[0037] A fermented traditional Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula, comprising the following raw materials in parts by weight: 20 parts Astragalus membranaceus, 15 parts Codonopsis pilosula, 12 parts Poria cocos, 10 parts Prunus mume, and 3 parts Lactobacillus acidophilus powder; wherein the viable count of the powder is 1×10⁻⁶. 9 CFU / g.

[0038] The preparation method of the above-mentioned fermented Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula includes the following steps: (1) Pretreatment of Chinese herbal raw materials: Astragalus membranaceus, Codonopsis pilosula, Poria cocos and Prunus mume were pulverized to less than 80 mesh, and then mixed evenly according to the above weight parts to obtain Chinese herbal mixed powder; 10 times the weight of deionized water was added to the Chinese herbal mixed powder, soaked for 3 hours, heated to boiling for 40 minutes, cooled to room temperature, filtered, and the filtrate was collected to obtain Chinese herbal extract. (2) Preparation of fermentation medium: Add 3% glucose, 1.0% peptone and 0.4% yeast extract by mass of the above Chinese herbal extract to the Chinese herbal extract, stir evenly, adjust the pH value to 6.5, sterilize at 121℃ and 0.1MPa for 30 min, cool to 37℃ to obtain fermentation medium; (3) Inoculation and fermentation: Add Lactobacillus acidophilus powder to the fermentation medium and ferment at 37°C under anaerobic conditions for 43 hours. Stir once every 8 hours during the fermentation process, and stir for 15 minutes each time. (4) Post-processing: After fermentation, the fermentation liquid was centrifuged at 4℃ and 8000r / min for 15min and the supernatant was collected; then it was freeze-dried under vacuum to obtain the fermented Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula.

[0039] Comparative Example 3 The difference between this comparative example and Example 1 is that the fermentation process is missing.

[0040] An unfermented Chinese herbal extract comprises the following raw materials in parts by weight: 20 parts Astragalus membranaceus, 15 parts Codonopsis pilosula, 12 parts Poria cocos, and 10 parts Prunus mume.

[0041] The preparation method of unfermented Chinese herbal extract includes the following steps: (1) Pretreatment of Chinese herbal raw materials: Astragalus membranaceus, Codonopsis pilosula, Poria cocos and Prunus mume were pulverized to less than 80 mesh, and then mixed evenly according to the above weight parts to obtain Chinese herbal mixed powder; 10 times the weight of deionized water was added to the Chinese herbal mixed powder, soaked for 3 hours, heated to boiling for 40 minutes, cooled to room temperature, filtered, and the filtrate was collected to obtain Chinese herbal extract. (2) Add 3% glucose, 1.0% peptone and 0.4% yeast extract by mass of the above Chinese herbal extract to the Chinese herbal extract, stir evenly, adjust the pH value to 6.5, sterilize at 121℃ and 0.1MPa for 30 min, and cool to 37℃. (3) Centrifuge the above solution at 4℃ and 8000r / min for 15min, collect the supernatant; then freeze dry under vacuum to obtain the unfermented Chinese herbal extract.

[0042] Comparative Example 4 The difference between this comparative example and Example 1 is that all strains were mixed and fermented.

[0043] The preparation method of the above-mentioned fermented Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula includes the following steps: (1) Pretreatment of Chinese herbal raw materials: Astragalus membranaceus, Codonopsis pilosula, Poria cocos and Prunus mume were pulverized to less than 80 mesh, and then mixed evenly according to the above weight parts to obtain Chinese herbal mixed powder; 10 times the weight of deionized water was added to the Chinese herbal mixed powder, soaked for 3 hours, heated to boiling for 40 minutes, cooled to room temperature, filtered, and the filtrate was collected to obtain Chinese herbal extract. (2) Preparation of fermentation medium: Add 3% glucose, 1.0% peptone and 0.4% yeast extract by mass of the above Chinese herbal extract to the Chinese herbal extract, stir evenly, adjust the pH value to 6.5, sterilize at 121℃ and 0.1MPa for 30 min, cool to 37℃ to obtain fermentation medium; (3) Inoculation and fermentation: Add Lactobacillus acidophilus powder, Lactobacillus reuteri powder and Lactobacillus casei powder to the fermentation medium and ferment at 37°C under anaerobic conditions for 43 hours. Stir once every 8 hours during the fermentation process, and stir for 15 minutes each time. (4) Post-processing: After fermentation, the fermentation liquid was centrifuged at 4℃ and 8000r / min for 15min and the supernatant was collected; then it was freeze-dried under vacuum to obtain the fermented Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula.

[0044] Comparative Example 5 The difference between this comparative example and Example 1 is that the fermentation sequence is different.

[0045] The preparation method of the above-mentioned fermented Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula includes the following steps: (1) Pretreatment of Chinese herbal raw materials: Astragalus membranaceus, Codonopsis pilosula, Poria cocos and Prunus mume were pulverized to less than 80 mesh, and then mixed evenly according to the above weight parts to obtain Chinese herbal mixed powder; 10 times the weight of deionized water was added to the Chinese herbal mixed powder, soaked for 3 hours, heated to boiling for 40 minutes, cooled to room temperature, filtered, and the filtrate was collected to obtain Chinese herbal extract. (2) Preparation of fermentation medium: Add 3% glucose, 1.0% peptone and 0.4% yeast extract by mass of the above Chinese herbal extract to the Chinese herbal extract, stir evenly, adjust the pH value to 6.5, sterilize at 121℃ and 0.1MPa for 30 min, cool to 37℃ to obtain fermentation medium; (3) Inoculation and fermentation: Add Lactobacillus casei powder to the fermentation medium and ferment at 37°C under anaerobic conditions for 25 hours. Stir once every 8 hours during the fermentation process, and stir for 15 minutes each time. Continue to add Lactobacillus acidophilus powder and Lactobacillus reuteri powder to the fermentation medium and ferment at 37°C under anaerobic conditions for 18 hours. Stir once every 8 hours during the fermentation process, and stir for 15 minutes each time. (4) Post-processing: After fermentation, the fermentation liquid was centrifuged at 4℃ and 8000r / min for 15min and the supernatant was collected; then it was freeze-dried under vacuum to obtain the fermented Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula.

[0046] Comparative Example 6 The difference between this comparative example and Example 1 is that the fermentation sequence is different.

[0047] The preparation method of the above-mentioned fermented Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula includes the following steps: (1) Pretreatment of Chinese herbal raw materials: Astragalus membranaceus, Codonopsis pilosula, Poria cocos and Prunus mume were pulverized to less than 80 mesh, and then mixed evenly according to the above weight parts to obtain Chinese herbal mixed powder; 10 times the weight of deionized water was added to the Chinese herbal mixed powder, soaked for 3 hours, heated to boiling for 40 minutes, cooled to room temperature, filtered, and the filtrate was collected to obtain Chinese herbal extract. (2) Preparation of fermentation medium: Add 3% glucose, 1.0% peptone and 0.4% yeast extract by mass of the above Chinese herbal extract to the Chinese herbal extract, stir evenly, adjust the pH value to 6.5, sterilize at 121℃ and 0.1MPa for 30 min, cool to 37℃ to obtain fermentation medium; (3) Inoculation and fermentation: Add Lactobacillus acidophilus powder and Lactobacillus casei powder to the fermentation medium and ferment at 37°C under anaerobic conditions for 18 hours. Stir once every 8 hours during the fermentation process, and stir for 15 minutes each time. Add Lactobacillus reuteri powder to the fermentation medium and ferment at 37°C under anaerobic conditions for 25 hours. Stir once every 8 hours during the fermentation process, and stir for 15 minutes each time. (4) Post-processing: After fermentation, the fermentation liquid was centrifuged at 4℃ and 8000r / min for 15min and the supernatant was collected; then it was freeze-dried under vacuum to obtain the fermented Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula.

[0048] Performance testing 1. To evaluate the therapeutic effect of a fermented Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula on a 3-day lincomycin hydrochloride-induced mouse diarrhea model.

[0049] (1) Experimental objective Through rigorous self-comparison and comparison, the effects of the fermented Chinese medicine compositions containing Astragalus membranaceus and Codonopsis pilosula prepared in Examples 1-3 and Comparative Examples 1-6 on improving intestinal motility in diarrhea model mice were verified.

[0050] (3) Experimental materials and animals Experimental animals: Healthy male KM mice, 6-8 weeks old, weighing 18-22g.

[0051] Test drug: Fermented traditional Chinese medicine compositions containing Astragalus and Codonopsis prepared in Examples 1-3 and Comparative Examples 1-6. Modeling drug: Lincomycin hydrochloride.

[0052] (4) Experimental procedure (a) Seven mice were acclimatized to standard laboratory conditions for three days. They were not fed on the afternoon of the third day. On the fourth day, baseline values ​​for normal defecation were determined. In the morning, each mouse was given physiological saline (0.2 mL / 10 g body weight) by gavage; the mice were immediately placed individually in cages lined with clean white paper.

[0053] (b) 5-11 day modeling stage: establishment of diarrhea model and determination of successful modeling Days 5 to 11 (7 consecutive days): Each morning, all mice were administered lincomycin hydrochloride by gavage (120 mg / kg). This was the modeling period. One hour after modeling, the mice were given normal food and water.

[0054] Criteria for successful model establishment (performed on day 11 after model establishment): Compared with the normal baseline value measured on day 4, the total number of fecal pellets in mice increased by more than 30% within 6 hours. The fecal state remained consistently loose or watery, without improvement within 24 hours. Both of these conditions must be met for the model to be considered successful. Mice with successful model establishment were formally included in the product efficacy experimental group. Mice that did not successfully establish a model were directly subjected to pathological sectioning and small intestinal propulsion rate analysis.

[0055] After the model was established, the mice were randomly divided into groups of 4. The experimental group received drug intervention, while the control group was fed normally every day until the end of the experiment.

[0056] (c) 12-18 day dosing phase Days 12 to 20 (10 consecutive days): Administer the drug daily via gavage (1200 mg / kg body weight), divided into two doses. During this period, discontinue lincomycin hydrochloride and allow the model mice to recover naturally. Mice were fed a normal diet and water supply. They were fed normally in the morning and at noon, and fasted in the afternoon of day 21.

[0057] Measurement of small intestinal propulsion rate: Small intestinal propulsion rate is a core quantitative indicator for evaluating the peristaltic function of the small intestine in mice. Its value directly reflects the contractile activity of small intestinal smooth muscle, the transit speed of intestinal contents, and the overall intestinal motility. The lower the propulsion rate, the weaker the small intestinal peristalsis and the better the drug efficacy.

[0058] 1. Prepare the tracer: Use 2% commercial ink.

[0059] 2. Animal preparation: Mice need to be fasted (fasted for 24 hours, but allowed free access to water) before the experiment to empty their intestines.

[0060] 3. Gavage administration: Mice were administered ink by gavage at a dose of 0.1 mL / 10 g body weight.

[0061] 4. Timing and euthanasia: Mice were euthanized by cervical dislocation 30 minutes after gavage.

[0062] 5. Anatomy and Measurement: Quickly open the abdominal cavity and separate the small intestine (from the pylorus to the ileocecal junction). Gently straighten the small intestine and measure the "total length of the small intestine" and the "length of ink advance" with a ruler. Calculate the propulsion rate: Calculate the small intestine propulsion rate according to the formula: Small intestine propulsion rate (%) = (ink advance length / total small intestine length) × 100%. At the same time, perform histological examination of colon tissue sections (HE section) on the mice.

[0063] The results are shown in Table 1.

[0064] Table 1 Performance Test Results

[0065] As shown in Table 1, the fermented Chinese medicine compositions containing Astragalus membranaceus and Codonopsis pilosula in Examples 1-3 had a better effect on improving intestinal motility in diarrhea model mice, and the mice also showed a significant increase in body weight.

[0066] In Comparative Example 1, the absence of two traditional Chinese medicine components, Poria cocos and Prunus mume, resulted in a decreased efficacy. Analysis suggests this is due to the loss of the synergistic effect of the herbal combination, coupled with the lack of the auxiliary components of Poria cocos polysaccharides and Prunus mume organic acids. Consequently, the survival and colonization rates of probiotics in the intestines decreased, making it unable to effectively inhibit the proliferation of harmful bacteria.

[0067] In Comparative Example 2, single probiotic fermentation using only Lactobacillus acidophilus failed to achieve the dual effects of intestinal mucosal repair and pathogenic bacteria elimination, and the effectiveness of the active components produced by fermentation was reduced.

[0068] In Comparative Example 3, the lack of fermentation process resulted in low bioavailability of the effective components of traditional Chinese medicine. Components such as astragaloside A in Astragalus membranaceus and codonopsis polysaccharides in Codonopsis pilosula could not be metabolized into small molecule active substances by probiotics. In the unfermented extract of traditional Chinese medicine, the large molecule components could not penetrate the intestinal mucosal barrier and could not effectively act on intestinal smooth muscle cells.

[0069] In Comparative Example 4, all bacterial strains were mixed and fermented. During mixed fermentation, Lactobacillus acidophilus, Lactobacillus casei, and Lactobacillus reuteri competed for carbon and nitrogen sources in the Chinese herbal extract. The dominant strains proliferated in large numbers, inhibiting the growth of the weaker strains and disrupting the synergistic network of the strains. At the same time, during mixed fermentation, the metabolic pathways of each strain were carried out simultaneously, resulting in excessively high concentrations of substances such as lactic acid and acetic acid, which irritated the intestinal mucosa.

[0070] The different fermentation sequences in Comparative Examples 5 and 6 resulted in an incompatible initial fermentation environment, limited strain activity, and weakened intestinal mucosal repair. Subsequent strains showed insufficient synergy, reduced metabolic activity, and were unable to effectively reduce intestinal motility, potentially leading to nutrient competition.

[0071] pass Figure 1-4 It can be seen that the therapeutic effects of the traditional Chinese medicine fermentation composition in Examples 1-2 on the pathological HE sections of mouse small intestine tissue were better than those in Comparative Examples 5 and 6.

[0072] The above description represents the preferred embodiments of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A Chinese medicine fermentation composition containing Radix Astragali and Radix Codonopsis, characterized in that, The traditional Chinese medicine fermentation composition comprises the following raw materials by weight: 10-30 parts of Huangqi, 10-25 parts of Dangshen, 8-20 parts of Fuling, 5-15 parts of Wumei, 0.5-2 parts of Lactobacillus acidophilus powder, 0.5-2 parts of Lactobacillus casei powder, and 0.5-2 parts of Lactobacillus reuteri powder; wherein the viable bacterial count of the Lactobacillus acidophilus powder, the Lactobacillus casei powder, and the Lactobacillus reuteri powder is all ≥1×10 9 CFU / g.

2. The Chinese medicine fermented composition containing radix astragali and radix codonopsis according to claim 1, characterized in that, The viable cell count of the Lactobacillus acidophilus powder, Lactobacillus casei powder and Lactobacillus reuteri powder is (1-5) x 10 9 CFU / g.

3. A method for preparing the Chinese medicine fermentation composition containing Huangqi Dangshen as claimed in claim 1, characterized in that, The method comprises the following steps: (1) Pre-treatment of Chinese medicine raw materials: Huangqi, Dangshen, Fuling and Wumei are respectively crushed and mixed uniformly to obtain a Chinese medicine mixed powder; Water is added to the Chinese medicine mixed powder, soaked, heated and boiled, cooled, filtered, and the filtrate is collected to obtain a Chinese medicine extract; (2) Preparation of fermentation medium: glucose, proteose peptone and yeast extract are added to the Chinese medicine extract, stirred uniformly, the pH value is adjusted, sterilized, and cooled to obtain a fermentation medium; (3) Inoculation and fermentation: Lactobacillus acidophilus powder and Lactobacillus reuteri powder are added to the fermentation medium, and anaerobic fermentation is carried out; then Lactobacillus casei powder is added to the fermentation medium, and anaerobic fermentation is continued; (4) Post-treatment: After fermentation, the fermentation broth is centrifuged, the supernatant is collected, and vacuum freeze-drying is carried out to obtain a Chinese medicine fermentation composition containing Huangqi and Dangshen.

4. The method for preparing the fermented traditional Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula according to claim 3, characterized in that, Glucose accounting for 2-5% of the mass of the Chinese medicine extract, 0.5-1.5% of proteose peptone, and 0.3-0.8% of yeast extract are added to the Chinese medicine extract.

5. The method for preparing the fermented traditional Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula according to claim 3, characterized in that, The pH value is adjusted to 6.0-7.

0.

6. The method for preparing the fermented traditional Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula according to claim 3, characterized in that, Lactobacillus acidophilus powder and Lactobacillus reuteri powder are added to the fermentation medium, and anaerobic fermentation is carried out at 35-38°C for 16-20h.

7. The method for preparing the fermented traditional Chinese medicine composition containing Astragalus membranaceus and Codonopsis pilosula according to claim 3, characterized in that, Lactobacillus casei powder is added to the fermentation medium, and anaerobic fermentation is continued at 35-38°C for 24-28h.

8. Use of the Chinese medicine fermentation composition containing Huangqi and Dangshen prepared by the preparation method of any one of claims 1-7 in the preparation of a drug for treating diarrhea.

9. The use of the Chinese medicine fermented composition containing Huangqi Dangshen according to claim 8 in the preparation of a medicine for treating diarrhea, characterized in that, The Chinese medicine fermentation composition containing Huangqi and Dangshen is used as an active ingredient, and a pharmaceutically acceptable excipient is added to prepare an oral preparation; the oral preparation includes powder, granules, capsules, tablets, and oral liquid.

10. The use of the Chinese medicine fermented composition containing Huangqi Dangshen according to claim 8 in the preparation of a medicine for treating diarrhea, characterized in that, The pharmaceutically acceptable excipient includes one or more of a filler, a disintegrant, a binder, a lubricant, a flavoring agent, and a preservative; wherein the filler is one or more of starch, lactose, and mannitol; the disintegrant is one or more of crospovidone and sodium carboxymethyl starch; the binder is one or more of povidone and hydroxypropyl methyl cellulose; the lubricant is one or more of magnesium stearate and talc; the flavoring agent is one or more of sucrose and stevioside; and the preservative is one or more of potassium sorbate and sodium benzoate.

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